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Farnesol Inhibits PI3 Kinase Signaling and Inflammatory Gene Expression in Primary Human Renal Epithelial Cells

Affiliation
Department of Geriatric Medicine, RWTH Aachen University Hospital, 52074 Aachen, Germany;(A.M.);(X.C.)
Müller, Aline;
ORCID
0000-0001-8989-3252
Affiliation
College of Pharmacy, Midwestern University, Glendale, AZ 85308, USA;(M.L.);(V.W.)
Lozoya, Maria;
Affiliation
Department of Geriatric Medicine, RWTH Aachen University Hospital, 52074 Aachen, Germany;(A.M.);(X.C.)
Chen, Xiaoying;
Affiliation
College of Pharmacy, Midwestern University, Glendale, AZ 85308, USA;(M.L.);(V.W.)
Weissig, Volkmar;
ORCID
0000-0003-4102-0748
Affiliation
Department of Geriatric Medicine, RWTH Aachen University Hospital, 52074 Aachen, Germany;(A.M.);(X.C.)
Nourbakhsh, Mahtab

Chronic inflammation and elevated cytokine levels are closely associated with the progression of chronic kidney disease (CKD), which is responsible for the manifestation of numerous complications and mortality. In addition to conventional CKD therapies, the possibility of using natural compounds with anti-inflammatory potential has attracted widespread attention in scientific research. This study aimed to study the potential anti-inflammatory effects of a natural oil compound, farnesol, in primary human renal proximal tubule epithelial cell (RPTEC) culture. Farnesol was encapsulated in lipid-based small unilamellar vesicles (SUVs) to overcome its insolubility in cell culture medium. The cell attachment of empty vesicles (SUVs) and farnesol-loaded vesicles (farnesol-SUVs) was examined using BODIPY, a fluorescent dye with hydrophobic properties. Next, we used multiple protein, RNA, and protein phosphorylation arrays to investigate the impact of farnesol on inflammatory signaling in RPTECs. The results indicated that farnesol inhibits TNF-α/IL-1β-induced phosphorylation of the PI3 kinase p85 subunit and subsequent transcriptional activation of the inflammatory genes TNFRSF9, CD27, TNFRSF8, DR6, FAS, IL-7, and CCL2. Therefore, farnesol may be a promising natural compound for treating CKD.

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